The objective of this proposal is to elucidate factors involved in the interactions of Leishmania donovani with its host cell, the hamster macrophage. The immediate aims will be to: (1) characterize the mechanism of promastigote-macrophage adhesion by identifying possible membrane receptors of macrophages for surface protein molecules of parasites; (2) probe the intralysosomal survival mechanism of amastigotes in macrophages; and (3) test the efficacy of lysosomotropic agents and of particulate carriers, e.g., liposomes, as drug delivery vehicles for antileishmanicydal effects. Experiments will be carried out in a culture system, which we developed recently. The rationale for the present proposal is based on our previous findings that indicated: (1) avid adhesion of promastigotes to the surface of macrophages and (2) the phagosome-lysosome fusion after the entry of amastigotes into macrophages. Specific assays and methods involving aspects of cell biology and biochemistry for most of the proposed studies have already been developed. The results of these studies will not only further our understanding of the basic mechanism of intracellular parasitism but also leads for more effective therapy of leishmaniasis.